Achondrogenesis, Type II

A 26-year-old pregnant woman was referred to the ultrasound unit at 26 weeks in her first pregnancy due to fetal short limbs. She had no family history of skeletal anomalies. 2D ultrasound revealed extremely short fetal limbs: femur 30mm (< 3rd percentile), tibia 24mm, fibula 23mm, humerus 28mm, ulna 28mm, radius 25mm, measurements consistent with 19 weeks of gestation assuming no bone fracture. There were bilateral clubfeet. No ossification of sacrum was seen on the sagittal section of the spine. There was no ossification of the cervical vertebral bodies. The fingers were short and the hands were swollen, without polydactyly. The ossification of the ribs was normal. The ossification of the calvarium was normal. The abdomen was prominent and chest appeared to be narrow with a champagne cork appearance. There was bilateral pyelectasis (9 and 10mm). Micrognathia was visible on the midline sagittal view of the face. Polyhydramnios was present with a mild subcutaneous edema. 3D ultrasound (surface rendering and X-ray mode) confirmed the previous findings and enhanced the visualization of the poor ossification of sacrum and cervical vertebral bodies, and showed thickened metaphyses. The presumptive diagnosis of achondrogenesis type II was made.

Bilateral pyelectasis

The narrow chest:

3D reconstruction of the spine and short ribs:

The absent sacrum:

The humerus and scapula, the arm:

The short leg:

The foot:

Micrognathia:

An amniocentesis was performed at this time and revealed a normal 46XY karyotype. Molecular genetic testing to detect mutation in the COL2A1 gene could not be performed.

Special sonographic features in the two distinct forms of achondrogenesis:

Hypochondrogenesis: absence of ossification limited to the cervical and sacral vertebrae and pubic bones often a cleft palate

The delivery occurred at 28 weeks, a stillborn male fetus of 1310 g, 29 cm long with a head circumference of 29 cm was delivered vaginally. Post-mortem evaluation of the fetus and the whole body roentgenogram (babygram) confirmed the diagnosis of achondrogenesis type II- hypochondrogenesis. The babygram showed an abnormal vertebral column with flat vertebral bodies and absent ossification in the sacral and upper cervical regions. The thorax was small with short ribs. The long tubular bones were shortened without metaphyseal spiking. The widened metaphyseal regions gave the humerus a dumbbell appearance. The pelvis was characterized by an absence of ossification of rhe pubis, hypoplastic iliac wings and flat acetabular roofs.

The X-rays:

DiscussionMore than 210 skeletal dysplasias are listed in The Gamut Index, among them: —19 are lethal or potentially lethal for the newborn (5). —50 are clinically apparent and identifiable at birth.—The prevalence of lethal skeletal dysplasias is 0.9 per 10,000 births (6). —Achondrogenesis occurs in approximately 6.4 in 100,000 births (7) and leads to death in utero or during the neonatal period.

The association of severe micromelia, small thorax and polyhydramnios were the initial clues to the diagnosis of a lethal skeletal dysplasia. Among the different signs that have helped us to distinguish between different lethal pathologies, the following sonographic features were the key findings that led us to suspect achondrogenesis type II :

1) The extreme micromelia2) The bilateral clubfoot3) The lack of vertebral ossification on cervical bodies and of the sacrum4) The micrognathia5) The aspect of generalized edema6) The normal appearance of the calvarium7) The absence of bone deformity or fractures

Achondrogenesis is the osteochondrodysplasia in which the bone length is most severely affected (8). Table I provides other parameters for the differential diagnosis of skeletal dysplasias (6, 9, 10). Up to now a few cases of achondrogenesis type II have been by antenatal sonography (11, 12, 13). Achondrogenesis type I, Parenti- Fraccaro type (20% of cases), can be distinguished from Achondrogenesis type II- Hypochondrogenesis (Langer-Saldino, 80% of cases) by some sonographic features (table II) (14, 1, 15).

Comparison of 2D and 3D prenatal sonograms and post-natal findings

In this case, the evaluation of the fetal spine by 2D ultrasound scanning suggested the diagnosis of achondrogenesis type II-hypochondrogenesis. There was no ossification of the sacrum (fig 1, fig 2), and although three vertebral ossification centers were present at every level of the thoraco-lombar spine (sonograms in parasagittal plane of the spine by moving the transducer), there was clearly a complete lack of ossification of cervical vertebral body centers in the sagittal plane when a longitudinal scan of the spine was performed.Despite Pretorius et al (9) suggesting that transverse scanning of the spine is extremely important to determine the number of ossification centers, in this case the transverse scanning was not conclusive. It should be emphasized that the sacrum is not ossified during the first trimester, so that the early diagnosis of hypochondrogenesis could not be offered on the basis of an under-ossification of the sacrum at this stage of pregnancy. The coronal view of the spine obtained with the 3D-X ray mode did not help us to specify the abnormalities. After birth, the babygram gave very similar information concerning the poor ossification of the sacrum and the absence of ossification of the cervical vertebral body. Nevertheless, 3D surface and volume rendering was clear in revealing the characteristic appearance of the face with micrognathia, shortening of the limbs, prominent abdomen, bilateral clubbed feet, fetal skin edema, and all that features were concordant with the gross appearance of the dead fetus.With 2D scanning, the bilateral clubfeet were obvious, but it was very difficult to obtain a good view of fetal face because of the polyhydramnios. This same polyhydramnios is however a great advantage in 3D surface rendering, allowing very clear pictures to be obtained. Even with a very meticulous prenatal examination, the definitive diagnosis has been made with the help of postnatal X rays. It was the babygram that revealed the typical features of hypochondrogenesis such as ossification of pelvic bones, the shape of vertebral bodies, the shape of ribs, the shape of iliac wings and the typical cupped or flared aspect of the metaphysis (in this case only establish on the humerus). It has been proposed (16) that MRI may provide the same type of information as those given by radiography plus additional information, for example the severity of the ossification defects. Our case illustrates the complementarity of 2D and 3D-prenatal ultrasound in making the diagnosis of achondrogenesis type II-hypochondrogenesis and their close concordance with the gross post-mortem appearance and the babygram.